Diagnostic imaging is an emerging technique in the field of medical equipment. For example, this technique is typically exploited for the assessment of blood perfusion, which finds use in several diagnostic applications and especially in ultrasound analysis. The perfusion assessment is based on the analysis of a sequence of ultrasound contrast images, obtainable by administering an ultrasound contrast agent (UCA) to a living subject. The contrast agent acts as an efficient ultrasound reflector, so that it can be easily detected applying ultrasound waves and measuring a resulting echo-signal. As the contrast agent flows at the same velocity as the blood in the subject, its tracking provides information about the perfusion of the blood in a body-part to be analyzed.
Suitable contrast agents include suspensions of gas bubbles in a liquid carrier. For this purpose, the gas bubbles are stabilized using emulsifiers, oils, thickeners or sugars, or by entraining or encapsulating the gas or a precursor thereof into a variety of systems. Stabilized gas bubbles are generally referred to as gas-filled microvesicles. The microvesicles include gas bubbles dispersed in an aqueous medium and bound at the gas/liquid interface by a very thin envelope involving a surfactant, i.e., an amphiphilic material (also known as microbubbles). Alternatively, the microvesicles include suspensions in which the gas bubbles are surrounded by a solid material envelope formed of natural or synthetic polymers (also known as microballoons or microcapsules). Another kind of ultrasound contrast agent includes suspensions of porous microparticles of polymers or other solids, which carry gas bubbles entrapped within the pores of the microparticles. Examples of suitable aqueous suspensions of microvesicles, in particular microbubbles and microballoons, and of the preparation thereof are described in EP-A-0458745, WO-A-91/15244, EP-A-0554213, WO-A-94/09829 and WO-A-95/16467, which are incorporated by reference.
The perfusion assessment process is typically implemented with the so-called destruction-replenishment technique. For this purpose, the body-part to be analyzed is first perfused with the contrast agent at a constant rate. The microbubbles are then destroyed by a flash of sufficient energy. Observation of the replenishment (or reperfusion) of the microbubbles in the body-part provides quantitative information about the local blood perfusion. For this purpose, the intensity of the echo-signal that is measured over time is fitted by a mathematical model, in order to extract quantitative indicators of blood perfusion; the information thus obtained can then be used to infer a physiological condition of the body-part. This technique has been proposed for the first time in Wei, K., Jayaweera, A. R., Firoozan, S., Linka, A., Skyba, D. M., and Kaul, S., “Quantification of Myocardial Blood Flow With Ultrasound-Induced Destruction of Microbubbles Administered as a Constant Venous Infusion,” Circulation, vol. 97 1998, which is incorporated by reference.
The above-described process has typically been borrowed from the indicator-dilution theory, which describes the time evolution of a concentration of an indicator as it is randomly diluted in a homogeneous medium. Indeed, prior investigators have been based their approach mostly on the intensity observed during the perfusion process, which is a quantity strongly determined by the so-called log-compression of the equipments that are generally used. This has led to the choice of a mathematical model consisting of a mono-exponential function I(t) (of the video gray level against time) with a general form given by:I(t)=A·(1−e−βt)where A is the steady-state amplitude, β is a “velocity” term of the mono-exponential function, and the time origin is taken at the instant immediately following the last destruction pulses. In the prior art (e.g., the cited articles by Wei et al.), the values A, β and Aβ have commonly been interpreted as quantities proportional to “blood volume”, “blood velocity” and “blood flow” within the body-part under analysis.
However, it has been observed that the known approach is very sensitive to the equipments used and to their settings (such as receiver gain, log-compression, and so on). Therefore, the perfusion parameters that are extracted cannot be compared between investigators using different equipments or settings. Furthermore, the perfusion parameters so obtained are only relative estimates, and are often not suitable for an absolute quantitative evaluation.
A further drawback of at least some of the solutions known in the art is that the above-described perfusion parameters (i.e., blood volume, velocity, and flow) can only provide an indication of the integrity of the tissue forming the body-part under analysis. These so-called haemodynamic parameters contain no information about the morphology of the micro-vascular network of the body-part (i.e., its configuration and structure). Therefore, available solutions may be ineffective in identifying pathologies that cause changes in the morphology of the vascularity of the body-part under analysis, with or without changes of its haemodynamic parameters.